important that i stay inside, a book i had to read or ... · • 1.1 million hiv + in u.s.; (36.9...

“But now I recall all the times when it was so

important that I stay inside, a book I had to read

or sometimes write, a game I had to watch on

TV. I was too busy so many times. So many

out-of-town trips, daddy-daughter dinners

missed at the school, dance recitals I had to

pass up.

And then we are out of time”……..

George Cantor; Sept., 1998

Back in the Day….Infectious Diseases Then and Now:

The Evolution of ID Strategies

G. Blackburn DO, MACOI

ACOI’s 77th Annual Convention and Scientific Sessions

Phoenix

October, 2019

• Disclosures: none

• Comments: my own (only slightly filtered)

Assassination of John F. Kennedy

November 22, 1963

1964

1968

1968(1955 -1975)

> 58,000 U.S. deaths

1.5 - 3.6 million total deaths

Assassination of Robert F. Kennedy

June 6, 1968

Assassination of Martin Luther King Jr

March 3, 1969

Stonewall Inn Riots

June 28, 1969

July 20, 1969

August 9, 1969

August 15-18,1969

CCOM 1969-1973

• My heroes:

• Ward Perrin DO “WEP”

• Steve Sokalski DO (Inf Dx)

• Michael James DO

• William Peppo DO

• Paul Benchwick DO

• Larry Haspel DO

• Tom Allen DO

• Don Hollingsworth DO

D.O.H. 1973-74

• My Heroes:

• Michael Opipari DO

• Michael Demattia DO

• James Beck DO

• Augie Perrotta DO

• Ronald Blonder DO

Botsford Hospital1974 - 1976

• the “Susser Group”, including

• David Susser DO (Cardiology)

• Michael Biederman DO (GI)

• Eugene Oliveri DO (GI)

• Larry Wickless DO (GI)

• Ray Gadowski DO (Cardiology)

• Chuck Tenner DO (Endocrine, Pulmonology)

• Bert Rabinowitz DO (Pulmonology)

• Joe Kessler DO (Nephrology)

• Morris Lieberman DO (Oncology)

• Paul Wenig DO (Rheumatology)

Wayne State University

Infectious Disease Fellowship

1976 - 1978

Reyes M et al.Pseudomonas Endocarditis in the Detroit Medical

Center. 1969-1972. Medicine 1973;52:173-194

• My Heroes:

• Ralph Cushing MD

• Carl Lauter MD

“You know nothing, G. Blackburn….”

Life before Antibiotics

• War casualties and other trauma

• Intra-abdominal catastrophes

• Bacterial meningitis

• Endocarditis

• Syphilis, gonorrhea

Vaccine Preventable Diseases -

Then

• measles

• mumps

• rubella

• diphtheria

• pertussis

• tetanus

• polio

• rabies (older version)

• smallpox

Vaccine Preventable Diseases -

Now

• measles

• mumps

• rubella

• diphtheria

• dengue

• pertussis

• tetanus

• influenza

• polio

• rabies

• hepatitis A

• hepatitis B

• pneumococcus

• smallpox

• ebola

• chlamydia (?)

• malaria (early)

• meningococcus /

H. influenza

• H. zoster (chickenpox)

• H. zoster (shingles)

• HPV

• Japanese encephalitis

• rotavirus

• typhoid

• cholera

Rabies

• Early 1900s (U.S.): ~100/yr

now: < 2/yr

• Worldwide: still 55,000/yr

• Prophylaxis back in the day……

21 painful intra-abdominal injections

• Now: 4 IM injections

Tetanus

• ~29 cases/yr (U.S.); 2 deaths

• Worldwide: still 59,000 deaths/yr

Vaccine “hesitancy” now listed as one

of top ten Global Health Threats for 2019

Polio (“infantile paralysis”) - early 1950s

Measles -

• ~1980: est. 2.6 million deaths/yr (worldwide)

• In the U.S., prior to 1963

• 2 - 4 million cases of measles

• 48,000 hospitalizations

• 4000 cases of encephalitis, 1/4 of which suffered life-long

disabilities

• 100 - 400 cases of SSPE

• 400 - 500 deaths (~1 in 10,000)(other references cite 1 - 2 in 1000)

• Worldwide, still kills over 90 - 120,000 (mostly)

children/yr; 400 deaths/day in 2013

• mortality may be as high as 1 in 10 in countries

where severe malnutrition is rampant

• infrequently seen in the U.S. and other advanced

countries until recently (1,182 cases as of 8/08/19)

• nearly 100% preventable

•Estimated 21,000,000 deaths prevented since

2000 by vaccination (Paules et al NEJM June 6, 2019)

Measles

Vaccine U.S. deaths/yr Deaths worldwide/yr

Hepatitis B < 2000 1,000,000

H. influenza < 5 199,000

Menningococcus 120 50,000

Measles < 1 > 90,000

Pertussis < 20 160,000

Pneumococcus < 22,000 826,000

Rotavirus < 10 215,000

Chickenpox < 20 > 4200

Polio 0 ? (but few)

Smallpox 0 0 (1967 - 5,000,000)

Newly Described or Newly Emerged

Infectious Diseases Since the Late ‘70s

• Acute Flaccid Myelitis

• Anaplasmosis

• Agents of Bioterrorism

• Chikungunya

• Candida auris

• C. difficile

• Chlamydia pneumoniae

• “Flesh-eating” Grp A

strep

• Antibiotic-resistant

gonorrhea

• Hanta virus

• HIV

• Legionnaire’s dx

• Lyme dx

• MDR GNRs

• MERS

• Erlichiosis

• MRSA, including “CA”

MRSA

• SARS

• TSS

• VRE

• West Nile

• XDR, MDR TB

• Zika

Newly Described or Newly Emerged

Infectious Diseases Since the Late ‘70s

• Hepatitis C

• Delta hepatitis

• Hepatitis E

• Hepatitis G (?)

• Marburg virus

• Lassa fever

• Ebola

• Prion dx

• Grp B strep

infections in adults

• Whipples

• H. pylori

• Post-splenectomy

sepsis

• Anaerobic

microbiology

• Pneumocystis

• Microsporidiosis

• Acanthameba

• Naegleria

• Babesiosis

• Cryptosporidium

• Cyclospora

SH Podolsky et al. N Engl J Med 2019;380:1785-1787.

Clostridium difficile

• Back in the day (1973-74)…..

• Tedesco F. - Clindamycin-Associated Colitis*

• 200 pts:

• 21% with diarrhea

• 10% pseudomembranous colitis

• 1978 - C. difficile identified as culprit

*Tedesco F. Clindamycin-Associated Colitis. Annals Int med. 1974;81(4):429-433

• Est. 453,000 cases (2011 data for U.S.)

• Est. 29,000 deaths

• Still problems with diagnostic testing

• Rx continues to evolve, including stool transplant

C. difficile

• 1960s-70s

• “Infectious” hepatitis (“A”)

• short incubation

• fecal - oral transmission

• highly contagious

• usually self-limited; no chronicity

• vaccine introduced (in U.S.) 1995

• 1960s-70s

• “Serum” hepatitis (“B”)

• discovered in 1965; vaccine available in 1981

• longer incubation

• parenteral or serum transmission

• less contagious

• chronic infection

• Hmmmmmm…. once testing became available, screening decreased

post-transfusion hepatitis by only 25 - 50%

Hepatitis C

• “Non A - Non B” hepatitis

• recognized as a major cause of post-transfusion hepatitis

• chronic hepatitis in 75% of cases, with progression to cirrhosis and liver

cancer

• early attempts at treatment ~ 1984

• finally isolated and described in 1989 -> “Hepatitis C”

• testing developed to remove from blood supply ~ 1990-1992

from Pawlotsky J-M, From non-A, non-B hepatitis to hepatitis C virus cure.

J. Hepatology 2015 (62): S97-S99

1986

• 1882: • Robert Koch described the etiologic agent of TB

• 1/3 of all infant deaths due to TB

• 1/2 of all deaths between the ages of 15-45 due to

TB

1851-1887

Back in the Day….

• TB was extremely common; in the early 1900s:

• ~80% of U.S. population infected by age 30

• Responsible for 1 of every 7 deaths in U. S.

• Note: PPD introduced ~ 1907 w/ multiple refinements since then; BCG introduced in 1906

• 70,000 deaths/yr (U.S.) in the 1930s; 547 in 2009

?

• As a health care worker, if your PPD is 10mm in

induration, you are a candidate for prophylaxis for

latent tuberculosis

• If 9 mm, you are not.

Why not?

What’s the difference?

Back in the Day….

• Treatment limited and often ineffective before the mid-1950s

• 1948 - Dr. Neal Browne, Minister of Health, Ireland:

• No physical activity; absolute bed rest

• Nutritious food; fresh air

• 2 pints of Guiness daily

• 1954 - INH (resistance now an issue, including MDR, XDR, prophylaxis)

Back in the Day……..

• Mass screening

• Mobile neighborhood Xray units

• Widespread use of Tine skin testing

• Surgical approaches to treatment

• Rib resection - “collapse” therapy

• Induced pneumothorax; plombage

• Lung resection

• Isolation - often for months or years

• Rx of 18 months or greater (even after 1954)

% of pts treated w/

“collapse therapy” (Canada)

Mond D and Khan A. N Engl J Med 1994;330:1723

Lucite-Ball Plombage

Currently:

• 1/4 of the world’s population is infected w/ M. tuberculosis (2,000,000,000+)

• 10 million persons newly infected each year

• 1.6 million die/yr from tuberculosis (300,000 HIV+)

• The #1 infectious cause of death; 25% of all preventable deaths

• ~ 641 kids children die/DAY of tuberculosis

Closer to home…

• 9,105 cases of active TB reported in U.S. (2017)

• 547 deaths from TB in U.S. (2009)

• Foreign born persons have 15 times greater likelihood of developing active TB*

• Asians greatest, but also • American Indians/Alaska Natives• Black/African American• Native Hawaiians/other Pacific Islanders

• Socioeconomic and genetic factors

Source: CDC June, 2019

Herpes Encephalitis

• Back in the day……..(~mid seventies and later)

• Hemorrhagic CSF (non-traumatic)

• Diagnosis: Brain biopsy (CSF culture negative)

• Treatment: Vidarabine (1976)

Herpes Encephalitis

• Currently…..

• Non-hemorrhagic CSF (especially when

obtained early) does not r/o this dx

• Diagnosis: PCR for HSV 1

• Treatment: Acyclovir

Sepsis

• Nebacumab (Centoxin ®): FDA approval denied

- 1992

• Drotrecogin alfa (Xigris ®): withdrawn from

marketplace - 2011

• Recombinant Human Soluble Thrombomodulin

(the SCARLET trial) JAMA (May 28,2019)

Somewhere between1902 - 1932

a deadly virus silently enters the human population

June 5, 1981 MMWR:

Pneumocystis Pneumonia - Los Angeles

“In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed P. carinii pneumonia at 3 different hospitals in Los Angeles, CA. Two of the patients died. All 5 patients had laboratory confirmed previous or current CMV infection and candida mucosal infection.”

What was causing this disease (almost exclusively w/in the gay community in the U.S.)?

• Drugs?

• A transmissible agent?

• Over next few years, found to be due to a virus initially labeled HTLV-III

• Brutal stigma from this diagnosis; also a death sentence - median survival w/ dx of AIDS: 12 -24 months

[see Frey J. You Have No Idea. JAMA 2011;306(5):469-470]

Gay is not a choice

Milestones:

• 1985 - Ab testing available for screening U.S. blood supply

• Late 1980’s/early 1990’s - single drug rx; however, very toxic, very inconvenient, with benefits lasting only a short time

• 1996 - recognition that triple drug “cocktails” were reasonably effective at controlling progression of disease while limiting rapid development of resistance

Downside: very high pill burden, many serious side effects

• 1.1 million HIV + in U.S.; (36.9 million worldwide)

• 1 in 7 unaware of their HIV +; many others in denial

• < 1/3 completely virally suppressed.

• 37,600 newly infected each year in U.S.; over 1/2

MSM - responsible for up to 30% of transmission!

• 38,000 newly diagnosed each year will present with

advanced disease (16,000 will die)

The Bad News:

• Extremely effective treatment w/ very minimal

side effects w/ a single pill/day!

• Post-exposure prophylaxis (PEP) effective!

• Pre-exposure prophylaxis (PrEP) effective!

• U = U !!!!

The Good News:

On Being a (good) Doctor

• Curiosity

• Learn the name of that dog (Safter T. The Name of the Dog. N Engl J Med. 2018;379:1299-1301

Brezina D. Alton Small. JAMA. 1998; 280(22):1902)

• The only lasting “legacy” you will leave behind is

what you have taught your students and have

done by example

Someday, you, and all those you

care about, will be a patient

How comfortable will you be if YOUR doctor turns

out to be someone you trained?

On Being a D.O.

• Back in the day……

• Perhaps as a result, we worked harder

• Perhaps also as a result, we are all bothers and

sisters - members of the same tribe…..

• We were different - are we still?

The Future

• Vaccines will continue to play a very important role in the prevention

of potentially deadly diseases (someday…a “universal” flu vaccine?)

• Antibiotic and antiviral options will, in some cases, be limited, while

in other cases be completely ineffective - there will be a greater role

for alternative/supplemental approaches to infection e.g. phage

therapy, manipulation of the microbiome (see below)

• The human microbiome will prove to be an amazing area of science

yet to be explored and understood

• But…only half of I.D. Fellowships fill

“So….Blackburn….What’s going to kill us

(and for which we are not prepared)?”

• Short of a global disaster, if you are

otherwise reasonably healthy, it’s the

common bugs that will kill most of us -

staph, strep, E. coli, pneumococcus,

influenza

• Nuclear war

• At the population level, an influenza-like

virus with a high mortality - pandemic

“Disease X” (think SARS)

• “When the Next Big One arrives........it will

be signaled first by quiet, puzzling reports

from faraway places - reports to which

disease scientists and public health

officials, but few of the rest of us, pay

close attention.” - D. Quammen. NYT 5/9/13

(Think “Reston” strain of Ebola, SARS

MERS, pandemic H1N1)

“So….Blackburn….What’s going to kill us

(and for which we are not prepared)?”

• Bioterrorist event - planned or unplanned

• Climate change, other environmental factors - change in range of

many organisms (e.g. Vibrio, Naegleria, C. auris), vectors

(Chaga’s dx, Zika), zoonoses

“….climate change is the greatest public health emergency of

our time and is particularly harmful to fetuses, infants,

children and adolescents”Salas R.N. et al. NEJM May 30, 2019

Thank you